Magnetic Resonance Imaging Cooling-Reheating Protocol Indicates Decreased Fat Fraction via Lipid Consumption in Suspected Brown Adipose Tissue

<div><p>Objectives</p><p>To evaluate whether a water-fat magnetic resonance imaging (MRI) cooling-reheating protocol could be used to detect changes in lipid content and perfusion in the main human brown adipose tissue (BAT) depot after a three-hour long mild cold exposure.</p><p>Materials and Methods</p><p>Nine volunteers were investigated with chemical-shift-encoded water-fat MRI at baseline, after a three-hour long cold exposure and after subsequent short reheating. Changes in fat fraction (FF) and R₂*, related to ambient temperature, were quantified within cervical-supraclavicular adipose tissue (considered as suspected BAT, denoted sBAT) after semi-automatic segmentation. In addition, FF and R₂* were quantified fully automatically in subcutaneous adipose tissue (not considered as suspected BAT, denoted SAT) for comparison. By assuming different time scales for the regulation of lipid turnover and perfusion in BAT, the changes were determined as resulting from either altered absolute fat content (lipid-related) or altered absolute water content (perfusion-related).</p><p>Results</p><p>sBAT-FF decreased after cold exposure (mean change in percentage points = -1.94 pp, P = 0.021) whereas no change was observed in SAT-FF (mean = 0.23 pp, P = 0.314). sBAT-R₂* tended to increase (mean = 0.65 s^-1, P = 0.051) and SAT-R₂* increased (mean = 0.40 s^-1, P = 0.038) after cold exposure. sBAT-FF remained decreased after reheating (mean = -1.92 pp, P = 0.008, compared to baseline) whereas SAT-FF decreased (mean = -0.79 pp, P = 0.008, compared to after cold exposure).</p><p>Conclusions</p><p>The sustained low sBAT-FF after reheating suggests lipid consumption, rather than altered perfusion, as the main cause to the decreased sBAT-FF. The results obtained demonstrate the use of the cooling-reheating protocol for detecting changes in the cervical-supraclavicular fat depot, being the main human brown adipose tissue depot, in terms of lipid content and perfusion.</p></div

Differences in fat fraction and R₂* between cervical-supraclavicular and subcutaneous adipose tissue at baseline.

<p>Measurements of (a) fat fraction (FF) and (b) R₂* in cervical-supraclavicular adipose tissue (considered as suspected brown adipose tissue, denoted sBAT) and subcutaneous adipose tissue (SAT) in individual subjects from the <i>Baseline MRI</i>. Values plotted correspond to volume of interest means.</p

Segmentation of cervical-supraclavicular and subcutaneous adipose tissue.

<p>A coronal (a) and axial (b) fat fraction (FF) map showing the manually delineated crude cervical-supraclavicular (considered as suspected brown adipose tissue, denoted sBAT) volume of interest (VOI) with a red contour, the final segmented sBAT VOI in green and the final segmented posterior subcutaneous adipose tissue (SAT) VOI in blue. Segmentation of the sBAT and SAT VOIs was accomplished by exclusion criteria on FF, R₂* and by erosion.</p

The <i>Cooling-reheating protocol</i> design.

<p>The <i>Cooling-reheating protocol</i> design.</p

Changes in fat fraction and R₂* of cervical-supraclavicular and subcutaneous adipose tissue during the <i>Cooling-reheating protocol</i>.

<p>Plots illustrating changes in (a) fat fraction (FF) and (b) R₂* of cervical-supraclavicular adipose tissue (considered as suspected brown adipose tissue, denoted sBAT) and subcutaneous adipose tissue (SAT). The fat fraction changes are expressed in percentage points (pp). The time points correspond to the <i>Baseline MRI</i> (t = 0), the <i>Cold MRI</i> (t = 3h) and the <i>Reheated MRI</i> (t = 3.5h). Values plotted represent group means (of individual volume of interest (VOI) means) and standard error of the group means. *p<0.05; **p<0.01; (ns) non-significant.</p

Changes in fat fraction (FF) and R₂^*.

<p>Note—Data on cervical-supraclavicular adipose tissue (considered as suspected brown adipose tissue, denoted sBAT) and subcutaneous adipose tissue (SAT) during the <i>Cooling-reheating protocol</i> (n = 9) and the <i>Procedure study</i> (n = 8). Result column 1–2: Measurements reported as group mean changes between the intra-protocol measurements with statistical significance of the changes given in parentheses. Fat fraction changes expressed in percentage points (pp). Result column 3: Statistical significance of differences between the changes obtained from the two protocols.</p><p>* p<0.05;</p><p>** p<0.01;</p><p>(ns) non-significant.</p><p>Changes in fat fraction (FF) and R₂<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0126705#t002fn002" target="_blank">^*</a>.</p

Summary of fat fraction (FF) and R₂* measurements.

<p>Note—Data on cervical-supraclavicular adipose tissue (considered as suspected brown adipose tissue, denoted sBAT) and subcutaneous adipose tissue (SAT) during the <i>Cooling-reheating protocol</i> (n = 9). Measurements reported as group means ± standard deviations (ranges) of individual volume of interest (VOI) means.</p><p>Summary of fat fraction (FF) and R₂* measurements.</p

Summary of estimates from the different types of analysis.

<p>Lines represent 95% CIs. CI, confidence interval; MR, Mendelian randomization; OR, odds ratio; SNP, single nucleotide polymorphism.</p

Association of childhood adiposity-related genetic variants with “ever smoker.”

<p>Lines represent 95% confidence intervals. Note that because of the large number of SNPs investigated, the threshold for nominal significance was set to <i>p</i> < 0.01. No SNP was alone associated with smoking, but the combined score showed a positive association. BMI, body mass index; CI, confidence interval; OR, odds ratio; SNP, single nucleotide polymorphism.</p

Association of adiposity-related genetic variants with childhood body mass index and type 1 diabetes.

<p>Association of adiposity-related genetic variants with childhood body mass index and type 1 diabetes.</p